title: Altered glycosylation of platelet-derived von Willebrand factor confers resistance to ADAMTS13 proteolysis.
abstract: Platelet-von Willebrand factor (VWF) is stored within α-granules and accounts for ∼20% of total VWF in platelet-rich plasma. This platelet-VWF pool is distinct from plasma-VWF and is enriched in high molecular weight multimers (HMWM). Previous studies have described significant functional discrepancies between platelet-VWF and plasma-VWF; however, the molecular basis of these differences is not well understood. We have characterized terminal glycan expression on platelet-VWF. Our findings demonstrate that platelet-VWF exists as a distinct natural glycoform. In particular, N-linked sialylation is markedly reduced (>50%) compared with plasma-VWF. Moreover, unlike plasma-VWF, platelet-VWF does not express AB blood group determinants, although precursor H antigen expression is similar to that on plasma-VWF. Because of this differential glycosylation, platelet-VWF exhibits specific resistance to ADAMTS13 proteolysis. Thus platelet activation at sites of vascular injury results in the release of high local concentrations of HMWM platelet-VWF that is more resistant to ADAMTS13, thereby facilitating platelet-plug formation.
authors.affiliation: Haemostasis Research Group, Institute of Molecular Medicine, Trinity Centre for Health Sciences, St James's Hospital, Trinity College Dublin, Ireland;
authors.forename: Rachel T
authors.initials: RT
authors.lastname: McGrath
authors.forename: Maartje
authors.initials: M
authors.lastname: van den Biggelaar
authors.forename: Barry
authors.initials: B
authors.lastname: Byrne
authors.forename: Jamie M
authors.initials: JM
authors.lastname: O'Sullivan
authors.forename: Orla
authors.initials: O
authors.lastname: Rawley
authors.forename: Richard
authors.initials: R
authors.lastname: O'Kennedy
authors.forename: Jan
authors.initials: J
authors.lastname: Voorberg
authors.forename: Roger J S
authors.initials: RJ
authors.lastname: Preston
authors.forename: James S
authors.initials: JS
authors.lastname: O'Donnell
mesh_terms: D000017:ABO Blood-Group System / Q000096:biosynthesis / Q000737:chemistry; D051722:ADAM Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000071120:ADAMTS13 Protein; D001777:Blood Coagulation / Q000502:physiology; D001792:Blood Platelets / Q000737:chemistry* / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D006031:Glycosylation; D057809:HEK293 Cells; D006801:Humans; D015539:Platelet Activation / Q000502:physiology; D059748:Proteolysis; D022142:Secretory Vesicles / Q000737:chemistry* / Q000378:metabolism; D014841:von Willebrand Factor / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D000017:ABO Blood-Group System; D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human